(Philadelphia,
PA) - Drugs designed to fight depression may also prevent
heart attacks, according to researchers at the University
of Pennsylvania Medical Center. In a large study of
smokers, the researchers associated a class of antidepressants,
called selective serotonin reuptake inhibitors (SSRIs),
with a lower heart attack risk. Their findings are published
in the latest issue of Circulation: Journal of the
American Heart Association.

"We found a 65 percent reduction in risk of a heart
attack among SSRI users compared to nonusers,"
said Stephen Kimmel, MD, associate professor of medicine
in the Penn Department of Biostatistics and Epidemiology
and the Cardiovascular Division of the Penn Department
of Medicine. "How it works is still unknown,
but we have reason to believe that, like aspirin, SSRIs
act to thin the blood and prevent clotting."

In the study, Kimmel and his colleagues compared people
in an eight-county region around the Philadelphia metropolitan
area who were hospitalized for a first heart attack
(653 people) with a randomly selected group of people
who had no history of a prior heart attack (2,990 people).
All patients in both groups were smokers.

Of the 143 SSRI users identified, 87 percent said they
were taking the drugs for depression; 3.5 percent for
anxiety and 9.1 percent for unknown or other indication.
Patients were studied over a 28-month period and were
between the ages of 30 and 65 years old. The SSRIs identified
in this study included fluoxetine (Prozac), fluvoxamine
(Luvox), paroxetine (Paxil) and sertraline (Zoloft).

"We actually collected this data for a study to
test the value of nicotine patches in preventing heart
attacks, since smoking is a high risk factor,"
said Kimmel. "In doing so we also collected detailed
information about the prescription drug use of participants
in the study."
The data Kimmel and his colleagues received allow them
to also compare the risk of heart attacks in people
who used antidepressants.

In addition to smoking, studies have also suggested
that depression may be a risk factor for heart disease
and is linked to a higher probability of death after
a heart attack. Earlier studies had suggested the association
between antidepressants and lower heart attack risk.
With the ready made pool of information, this study
became the largest of its kind to examine whether SSRIs
prescribed for depression lowered the risk of a first
non-fatal heart attack.

The researchers were not, however, able to directly
determine from the data how SSRIs may protect from heart
attack. According to Kimmel, the study could not distinguish
between whether the beneficial effects of treating depression
reduced the risk of heart attack or if it was the SSRIs'
pharmacological effects. As devised, the study did not
involve the use of validated depression scales, which
are used to assess the severity of depression - and
therefore were unable to reach a definitive conclusion.

Tentatively, Kimmel and his colleagues theorize that
the drugs might protect the heart the same way aspirin
does, by preventing platelets, the parts of the blood
that form clots, from clumping together. The majority
of heart attacks are caused by blood clots.

The researchers believe that a randomized controlled
trial study of significant size would be necessary to
make a definitive link between SSRIs and preventing
heart attacks. They also suggest that other forms of
antidepressant medications aside from SSRIs be taken
into account to determine if they may have a similar
effect.

"However provocative, these are just preliminary
findings," said Kimmel. "We did not start
out looking at this problem, exactly, but it does provide
a springboard for further research - both statistically,
such as ours, and in the laboratory."

Penn researchers, William H. Sauer, MD, and Jesse
A. Berlin ScD, were co-investigators in this project.
Funding for this study was provided by Aventis Pharmaceuticals,
Novartis Consumer Health, and McNeil Consumer Products
Co.

The University of Pennsylvania Health System is distinguished
not only by its historical significance - first hospital
(1751), first medical school (1765), first university
teaching hospital (1874), first fully integrated academic
health system (1993) - but by its position as a major
player on the world stage of medicine in the 21st century.
Committed to a three-part mission of education, research,
and clinical excellence, UPHS has excelled in all three
areas. Penn ranked second among all American medical
schools that received funds from the National Institutes
of Health, perhaps the single most important barometer
of research strength.